In the earliest parts of US history, American policy was to remove and relocate Indians to places where they would be allowed to simply live independently. This was done when there were still large areas of land outside the settled US where the Indians could be sent.
Later on, these open spaces disappeared with westward expansion. When that happened, it was necessary to put Indians on reservations. There, they would be separated from whites but would be controlled in ways that they could not be controlled before.
Finally, there was a move to a policy of assimilation as Americans came to believe they needed to "improve" the Indians rather than simply getting rid of them. This policy was meant to "kill the Indian to save the man." It was not incompatible with the reservation policy. Instead, it was an addition to that policy.